In recent years, polyphenols contained in tea and wine have been attracting attention for various physiological activities. Among polyphenols, flavan compounds (for example, catechin) having flavan-3-ol as a mother nucleus structure have been long known as compounds exhibiting strong antioxidant properties. Furthermore, more recently, it has been revealed that flavan compounds have important physiological actions, such as antitumor action, antiviral action, anticavity action, and blood pressure lowering action. Hence, expectation for the application to the field of medicine has been rising.

Regarding the biosynthetic pathway of flavan compounds, a theory using chalcone as a precursor as described below is compelling. Based on this, it is considered that involvement of various processes such as oxidation, reduction, rearrangement, and/or isomerization, in combination leads to the formation of a wide variety of analogs having different numbers and binding positions of oxygen functionalities.

However, due to similarities in the structures of flavan compounds, it is difficult to obtain a single flavan compound from nature by isolation and purification. Against such a background, synthesis of flavan compounds has been actively investigated. Although flavan compounds have relative simple structures, only a few synthesis examples have been reported.
For example, Zaveri et al. reported synthesis of gallocatechin derivatives by simultaneously performing reduction of the carbonyl group in a chalcone derivative and formation of a ring followed by a hydroboration reaction of olefin (refer to Non Patent Document 1). However, this method still has a problem that it is impossible to freely control relative configurations at the 2- and 3-positions, since stereoselectivity in the hydroboration reaction of olefin is determined by the presence of aromatic rings.

Meanwhile, Ferreira et al. reported synthesis of flavan derivatives by asymmetric dihydroxylation of (E)-olefin derivative derived from chalcone to introduce a chiral center corresponding to the 3-position of a flavan derivative, followed by dehydrative cyclization reaction under acidic condition (refer to Non Patent Document 2). However, this method has a problem regarding stereochemical control. More specifically, this method does not have high stereoselectivity in the dehydrative cyclization reaction, and thereby provides two kinds of diastereomer.

Furthermore, Hyeung-Geun Park et al. reported stereoselective synthesis of flavan derivatives by using caffeic acid and a phloroglucinol derivative (refer to Non Patent Document 3). In this method, an aldehydes body obtained from caffeic acid going through several steps, such as asymmetric dihydroxylation, is coupled with a lithiated phloroglucinol derivative to give an intermediate having a necessary carbon backbone. Then, after being subjected to further conversion, the obtained intermediate forms a pyran ring by the Mitsunobu reaction, and a flavan derivative is obtained. Although a flavan derivative having a desired stereochemistry can be obtained by this method, there is a problem in yields of the key reactions, the coupling reaction with a phloroglucinol derivative and the pyran ring formation by the Mitsunobu reaction. Therefore, this method is hardly an effective method.

[Non Patent Document 1] Zaveri et al., Organic Letters, 3, pp. 843-846 (2001)
[Non Patent Document 2] Ferreira et al., Tetrahedron Letters, 38, 3089-3092 (1997)
[Non Patent Document 3] Hyeung-Geun Park et al., Tetrahedron Asymmetry, 13, 715-720 (2002)
[Non Patent Document 4] Zu et al., Tetrahedron Asymmetry, 11, pp. 2801-2809 (2000)